The positive association between the serum lipid levels and the incidence of atherosclerotic cardiovascular disease requires no further proof of causality. What does require further and conclusive documentation is the converse of the lipid level atherosclerosis hypothesis: Does a reduction of elevated lipids bring about a reduction of atherosclerotic risk? Application of the scientific method to this question would start with a test of maximum obtainable lipid level reduction. If maximum lipid lowering does not influence the development of progression of atherosclerosis then it is unlikely that less than maximum lipid lowering will have a positive effect. We, therefore, propose the establishment of multi-centered randomized primary and secondary prevention trials utilizing the partial ileal bypass operation and supported by a central lipid laboratory, a central data processing facility, and an associated research program. Partial ileal bypass is chosen as the principal therapeutic procedure since it offers the following unique advantages in the management of the hyperlipidemias: (1) it is the most effective means of reducing lipid levels available today (e.g. 40% cholesterol lowering following maximum type specific dietary therapy, 53% cholesterol lowering in association with diet in type II hyperlipoproteinemic patients, 68% triglyceride lowering post maximum type specific dietary management); (2) it is a lasting means of management (no rebound in over eight years experience); (3) it is safe (less than 1% in-hospital mortality); and (4) it is obligatory upon the patient and thereby aids investigation of its action by not requiring patient cooperation.